The proposed research is a long-term, broad attack on several interrelated problems in human population genetics. Theoretical and methodological studies develop and apply mathematical models to pedigree analysis (including complex segregation of genetic disorders and quantitative traits, recurrence risks for genetic counseling, parentage exclusion, mutation screening, zygosity, and linkage), population structure (kinship and hybridity), the role of neutral mutation in polmorphism and protein evolution, and the formal genetics and effects on health of chromosomal polymorphisms and abnormalities. Field studies using these models are directed to mental retardation and hyperlipemia in Hawaii and chromosomal polymorphisms, idiomorphs, and kinship in various ethnic groups. In designating this laboratory its International Reference Center for Processing of Human Genetics Data, the World Health Organization has provided a flow of visiting investigators who come to use the core facilities (computers, programs, and consulting staff) and to compare their results with those of the resident investigators. Other members of the biomedical faculty at the University of Hawaii also use these facilities for described research on cancer, heart diseases, dental anomalies, and leprosy.